Among multicomponent polymers, an interpenetrating polymer network ("IPN") is the sole macromolecule synthesized through cross-linking, which is a mixture of more than two macromolecular, physically interwound cross-linked structure, having different characteristics such as hydrophilicity/hydrophobicity. So far, it has been reported that an IPN with hydrophobicity/hydrophobicity has a sea-island phase separation structure with excellent properties, which can be controlled to be a co-continuous morphology by changing synthetic temperature or pressure (see: S. S. Lee and S. C. Kim, Polymer (Korea), 10(3);236(1986); S. K. Kim and S. C. Kim, Polymer Bulletin, 23:141(1990)). Accordingly, on the ground that the IPN with hydrophilicity/hydrophobicity has excellent material properties and its hydrophilic/hydrophobic phase separation structure shows blood compatibility, it has been proposed as a promising biomaterial used for the direct contact part with blood.
The IPN can be prepared by the following two polymerization methods: Sequential polymerization method comprises the steps of synthesizing a cross-linked macromolecule A, and allowing polymerization and cross-linking of monomer B in a swelled macromolecule A; and, simultaneous polymerization method comprises the steps of mixing monomer A and B, non reactive each other (e.g., A is a monomer cross-linked through the reaction of free radical by double bond, while B is a monomer condensate-polymerized through functional reaction at the end of B), and synthesizing cross-linked macromolecules A and B in a simultaneous and independent manner. In the IPN, more micro dispersion state can be obtained, since cross-linking structures of two macromolecules are physically interwound to inhibit further phase separation, when polymerization of monomers reaches at the gelation point. Further, spinodal or co-continuous structure can be obtained, if the phase separation is suppressed in the early stage.
In general, phase separation occurs at multicomponent polymers, since polymers with more than two different properties are linked each other. This phase separation is a critical factor affecting properties of material, which is affected mainly by chemical structure, composition and manufacturing process of macromolecules. Also, IPN, a multicomponent polymer, shows a phase separation structure which is controlled by miscibility, cross-linking density, reaction velocity, mobility of macromolecular chain, etc.
On the other hand, there have been attempts to develop materials inhibiting thrombogenesis, since antithrombogenecity is the most important characteristic in the field of artificial blood vessel which is directly contacted with blood. The macromolecular surface affecting blood compatibility is changed largely by physical and chemical structure. In this connection, studies on blood compatibility have been actively carried out in light of polarity, surface energy, degree of hydrophilicity/hydrophobicity and so on. When the macromolecular surface comes to contact with blood, thrombus is finally formed on the surface. Although the process of thrombogenesis is not clearly known at present, it is generally accepted that when macromolecular surface comes to contact with blood, plasma protein immediately adsorbs on the surface and the adsorbed protein interacts with platelet, which is directly or indirectly related with the thrombogenesis through agglutination of platelet, modification and aggregation. In short, the macromolecular characteristic plays a very important role in interaction of macromolecule, which accelerates the studies on the effect of hydrophilicity/hydrophobicity of the macromolecular surface.
For example, U.S. Pat. Nos. 4,687,831 and 4,675,361 disclosed the use of block co-polymer in the linking of hydrophilicity and hydrophobicity and hard and soft chain. Also, Okano et al. reported that blood compatibility of block co-polymer consisted of hydrophilic poly(2-hydroxyethyl methacrylate) and hydrophobic polystyrene is related with the composition change of the hydrophilic component (see: T. Okano et al., J. Biomed. Mater. Res., 15:393)1982)). Moreover, Shimada et al. reported the blood compatibility depending on the composition change of block co-polymer of hydroxyethylmethacrylate-dimethylsiloxane (see: M. Shimada et al., Polymer J., 15:649(1983)).
However, the conventional hydrophilic/hydrophobic block co-polymers have been proven to be less satisfactory in a sense that they do not provide sufficient blood compatibility in light of mechanical properties and maintenance of phase separation structure.
In this regard, the inventors have tried to improve the blood compatibility, based on Okano et al's hypothesis that blood compatibility of the hydrophilic/hydrophobic microphase separation surface is closely related with the selective adsorption of plasma protein on the macromolecular surface (see: T. Okano et al., J. Biomed. Mater. Res., 15:393(1981)). Antithrombogenesis by the selective adsorption of plasma protein on the macromolecular surface has a significance that: among plasma proteins, albumin comes to be adsorbed on the hydrophilic part, while fibrinogen and gamma-globulin comes to be adsorbed on the hydrophobic part, and the adsorbed plasma protein becomes the textured structure controlled by the hydrophilic/hydrophobic microphase structural surface, which results in the inhibition of activation of platelet. In this regard, the factors affecting agglutination and activation of platelet in the hydrophilic/hydrophobic microphase structure are the balance of hydrophilicity and hydrophobicity in the macromolecular surface and the morphology and the size of hydrophilic/hydrophobic microphase. Actually, normal epithelial cells of blood vessel having ideal antithrombogenesis have the microphase separation structure consisted of hydrophilicity/hydrophobicity.
Accordingly, there are strong reasons for exploring and developing a method for improving the blood compatibility of polymers by controlling various factors affecting the platelet agglutination.